A variety of experimental evidence supports a role for alterations in the sensitivity of brain neurotransmitter receptors in the etiology of certain psychiatric diseases. This proposal concerns the assessment of neurotransmitter receptor sensitivity of psychiatric patients using peripheral blood elements. Receptor studies will be conducted using ligand-binding techniques and cAMP production. We plan to study three groups of psychiatric patients. The receptors to be studied in each group of patients are chosen to reflect hypotheses about the roles of various neurotransmitters in each disorder. Patients with schizophrenia will have an assessment of blood cell dopamine, histamine and prostaglandin receptors. We will also examine whether dopamine receptor sensitivity in lymphocytes of schizophrenic patients is a useful predictor of treatment response to haloperidol. Patients with major depressive episode will have assessments of blood cell norepinephrine, histamine, and acetylcholine receptors, and of the platelet serotonin-reuptake mechanism. Patients with Alzheimer's disease will have an assessment of leukocyte muscarinic receptors, and we will examine whether this parameter is a useful predictor of treatment response to muscarinic agonists. We plan to determine if alterations in blood cell neurotransmitter sensitivity have value as biological trait markers for these three psychiatric disorders. Receptor sensitivity will also be assessed in blood elements of schizophrenic and depressed patients in the exacerbated and remitted states of their illness, permitting an identification of possible state-dependent biological markers. These data will be analyzed together with data from other research studies concerning phenomenology, other biological measurements, and pharmacological treatment response of psychiatric patients. We hope that this analysis will aid in the identification of more homogeneous subgroups of patients with psychiatric disorders by biological criteria, that may be validated by non-biological measures.